Environmental and Occupational Disorders
Glutathione S-transferase GSTP1 is a susceptibility gene for occupational asthma induced by isocyanates,☆☆,

https://doi.org/10.1067/mai.2002.123234Get rights and content

Abstract

Background: Polymorphism at the π class glutathione-S-transferase locus (GSTP1) is associated with allergen-induced asthma and related phenotypes. Objective: We sought to determine whether GSTP1 polymorphism influences susceptibility to asthma induced by toluene diisocyanate (TDI). Methods: The role of GSTP1 was assessed in 131 workers exposed to TDI, 92 with TDI-induced asthma and 39 asymptomatic subjects. The phenotype of the disease was characterized by using detailed clinical history, lung volumes, airway responsiveness to methacholine, and airway responsiveness to TDI. GST genotypes were determined by using PCR-based assays. Results: In patients exposed to TDI for 10 or more years, the frequency of the GSTP1 Val/Val genotype was lower in subjects who had asthma (odds ratio, 0.23; 95% confidence interval, 0.05-1.13; P = .074). Similarly, the frequency of this genotype was significantly lower in subjects with evidence of moderate-to-severe airway hyperresponsiveness to methacholine compared with the frequency in subjects with normal or mild hyperresponsiveness (P = .033). Conclusion: These data suggest that homozygosity for the GSTP1*Val allele confers protection against TDI-induced asthma and airway hyperresponsiveness. This view is supported by the finding that the protective effect increases in proportion to the duration of exposure to TDI. (J Allergy Clin Immunol 2002;109:867–72.)

Section snippets

Subject recruitment

The association between GST genotypes and susceptibility was studied in 131 unrelated white European subjects residing in the north of Italy. All were exposed to TDI in furniture or body shops. The 92 asthmatic patients were recruited in the Department of Environmental Medicine and Public Health of the University of Padua, which was established to diagnose occupational asthma induced by exposure to isocyanates. The 39 asymptomatic workers were employed in the same factories for at least 10

GSTP1 genotype frequencies

Table II shows GSTP1 genotype frequencies in the study population. Frequencies of the GSTP1*A, GSTP1*B, GSTP1*C, and GSTP1*D alleles were 0.694, 0.177, 0.069, and 0.044, respectively. GSTP1 genotype frequencies achieved Hardy-Weinberg equilibrium and were similar to those observed in a population of atopic asthmatic subjects, atopic nonasthmatic subjects, and nonatopic asthmatic subjects from North Staffordshire, England, except that the GSTP1*D frequency (0.005) was lower.14

Association ofGSTP1 genotypes with asthma and AHR

GSTP1 genotype

Discussion

We have shown that polymorphism in GSTP1 is associated with susceptibility to asthma induced by prolonged exposure to TDI, a commonly used occupational respiratory sensitizer. We have also demonstrated that homozygosity for the Val 105-encoding alleles confer protection against the development of the asthma-associated phenotype AHR; this protective effect increased in proportion to the duration of TDI exposure. Our data suggest that individuals lacking this genotype may, over time, exhibit

Acknowledgements

We thank Stefano Ferrarese, MD, for his valuable contribution.

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    Supported by MURST (60% and 40%), Ministero del Lavoro e della Previdenza Sociale, ARCA, and the British Lung Foundation.

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    Reprint requests: Cristina E. Mapp, MD, Dipartimento di Medicina Clinica e Sperimentale, Sezione di Igiene e Medicina del Lavoro, Via Fossato di Mortara 64/b, 44100 Ferrara, Italy.

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